setrobuvir (AN598) / Roche - LARVOL DELTA

Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an in silico perspective. (PubMed, Future Microbiol) - "The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before. Additionally, other compounds such as setrobuvir, YAK, IDX-184 and modified GTP compounds 2, 3 and 4 show potential calculated average binding affinities against R. oryzae RdRp. The present in silico study suggests the dual inhibition potential of the recommended drugs and compounds against SARS-CoV-2 and R. oryzae RdRps."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

INSIGHTS INTO THE BIOLOGICAL IMPACT OF COVID-19 AND ITS VACCINES ON HUMAN HEALTH. (PubMed, Saudi J Biol Sci) - "The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection. RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time. Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use...Top seeds for antiviral treatments with high potential to combat the SARS-CoV-2 strain include guanosine derivatives (IDX-184), setrobuvir, and YAK. The goal of this review is to compile scattered information on available COVID-19 vaccines and other treatments for protecting the human body..."

Journal • Review • Cardiovascular • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antiviral drugs against severe acute respiratory syndrome coronavirus 2 infection triggering the coronavirus disease-19 pandemic. (PubMed, Tzu Chi Med J) - "The nucleotide inhibitors such as sofosbuvir, ribavirin, galidesivir, remdesivir, favipiravir, cefuroxime, tenofovir, and hydroxychloroquine (HCHL), setrobuvir, YAK, and IDX-184 were found to be effective in binding to SARS-CoV-2 RNA-dependent RNA polymerase. From the antimalarial and anti-inflammatory category, chloroquine and its derivative HCHL have already been approved by the U.S. Food and Drug Administration for emergency treatment of SARS-CoV-2 infection. The other drugs such as favipiravir and lopinavir/ritonavir under the antiviral category, the angiotensin-converting enzyme 2 (the renin-angiotensin system inhibitors), remdesivir (RNA polymerase inhibitor) from antiviral category, cepharanthine from anti-inflammatory category, etc., have been pointed based on the previous literature published. Besides, the assessment of the drug repositioning candidates with the related targets is also significant for the viral mitigation."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. (PubMed, Life Sci) - "The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: An in silico perspective. (PubMed, J Biomol Struct Dyn) - "The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp. Additionally, Setrobuvir, YAK, and IDX-184, show better results, while four novel IDX-184 derivatives show promising results in attaching to the SARS-CoV-2 RdRp...The availability of a punch of FDA-approved anti-viral drugs can help us in this mission, aiming to reduce the danger of COVID-19. The compounds 2 and 3 may tightly bind to the SARS-CoV-2 RdRp and so may be successful in the treatment of COVID-19."

Journal • Immunology • Novel Coronavirus Disease

Roche pipeline updated (Roche Press Release) - Anticipated NME submission in EU and US for hep C infection in 2017 or later for mericitabine and danoprevir; Anticipated regulatory submission for hep C infection for setrobuvir in 2016.

Anticipated EU regulatory • Anticipated NDA • Anticipated regulatory • Hepatitis C Virus

Molecular modeling and residue interaction network studies on the mechanism of binding and resistance of the HCV NS5B polymerase mutants to VX-222 and ANA598 (Antiviral Res) - "Molecular dynamics (MD) simulations results combined with binding free energy calculations indicated that the mutations significantly altered the binding free energy and the interaction for the drugs to polymerase. The further per-residue binding free energy decomposition analysis revealed that the mutations decreased the interactions with several key residues, such as L419, M423, L474, S476, I482, L497, for VX-222 and L384, N411, M414, Y415, Q446, S556, G557 for ANA598."

Preclinical • Hepatitis C Virus

SVR12 rates achieved with all-oral interferon-free regimens containing setrobuvir in combination with ritonavir-boosted danoprevir and ribavirin with or without mericitabine in HCV genotype 1 treatment-naive patients: Results from the ANNAPURNA study (APASL 2014) - Abstract #519; P2, N=110; ANNAPURNA (NCT01628094); Sponsor: Hoffmann-La Roche; "The ANNAPURNA study demonstrates that a 14-week all-oral regimen of STV + DNVr + MCB + RBV...produced an SVR12 rate of 96% in G1b patients, while a 26-week all-oral regimen (including a 2-week LI) produced an SVR12 rate of 70% in G1a patients."

P2 data • Hepatitis C Virus

Interferon-free regimen containing setrobuvir (STV) in combination with ritonavir-boosted danoprevir (DNVr) and ribavirin (R) with or without mericitabine (MCB) in HCV genotype (G)1 treatment-naive patients: interim SVR4 results from the ANNAPURNA study (AASLD 2013) - Presentation time: Sun, Nov 03, 2013; 8:00 AM - 5:30 PM; Abstract#1098; P2, N=110; ANNAPURNA (NCT01628094); "End of treatment (EOT) response was observed in all G1b patients (45/45), and in most of the G1a patients (7/7 of those who received 14wks of therapy, and 42/47 of those who received 26wks of therapy). For G1a patients, the overall SVR4 rate was 74% for patients receiving 26wks of therapy compared with 43% for those receiving 14wks of therapy. For G1b patients, the SVR4 rate was 96% among patients receiving 3 DAAs+R versus 77% among those receiving 2 DAAs..."

P2 data • Hepatitis C Virus

Roche: Late-Stage Pipeline Event (Roche) - Anticipated regulatory submission in EU for hep C infection in 2016 or after; Anticipated regulatory submission in US for hep C infection in 2016 or after

Anticipated EU regulatory • Anticipated FDA event • Hepatitis C Virus

Anadys announces positive 12-week data for setrobuvir in phase 2b hepatitis C study (PRNewswire) - P2b, N=283; 78% of treatment-naive pts & 76% of pts who had responded inadequately to, or relapsed after, prior treatment with P/R had undetectable virus at wk 12 (cEVR) while receiving setrobuvir plus P/R, compared to 56% & 44%, respectively, for patients who received placebo plus P/R; 71% of treatment-naive pts who had received setrobuvir plus P/R had undetectable virus at wk 8 & had met the initial response-guided criteria for shortening treatment in this study to 28 wks from the traditional 48 wks for treatment with P/R alone; 29% of pts who had no appreciable response to prior treatment with P/R (null responders) had achieved cEVR with setrobuvir plus P/R, & percentage of pts with undetectable virus continued to climb in this hard-to-treat population to 36% at wk 18

P2b data • Hepatitis C Virus

A pharmacokinetic/viral kinetic model to evaluate treatment of chronic HCV infection with a non-nucleoside polymerase inhibitor. (PubMed, Antivir Ther) - "Understanding the combined effects of PK/VK on the performance of a non-nucleoside polymerase inhibitor such as setrobuvir could provide valuable insights into their use in combination with other DAAs as well as to optimize future therapy. Further, our work suggests that patients infected with subtype 1a would need higher doses than those infected with subtype 1b to achieve the same effectiveness. Whether this is true for other non-nucleoside polymerase inhibitors needs to be examined."

Journal • PK/PD data